The effect on BP of 100 and 200 mg spironolactone/day has been compared with that of methyl-dopa, 750 mg/day, and with combined treatment with both drugs in 32 patients with essential hypertension. The 28 patients who completed the entire investigation were treated for 30 weeks, divided into 4 treatment periods and 4 placebo periods of equal duration. BP did not fall significantly during the initial placebo period, and at the end of each of the intervening placebo periods it rose to pretreatment levels. A signifcant decrease in mean BP was found during the 4 treatment periods. A fall exceeding 14% was registered in 32% of the patients after methyldopa, 750 mg/day, in 50% of the patients after spironolactone, 200 mg/day, in 89% after combined treatment with both drugs, and in 29% after spironolactone, 100 mg/day. Low renin hypertension was found in 9 of the 28 patients. The average decrease in mean BP after sironolactone, 200 mg/day, methyldopa, 750 mg/day, and after combined treatment did not differ significantly between the low and the normal renin group. The rationale for using diuretics such as spironolactone or thiazide as the basic therapy in essential hypertension is discussed. It is concluded that both are useful in the treatment of essential hypertension and might be used alone or in combination.